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ARDS and Ventilator Management
Behrouz Jafari, M.D.
Pulmonary & Critical Care Section
University of California-Irvine/VA Long Beach
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27-year-old woman with dyspnea
• 4 days s/p C-section
• Gradual increase in dyspnea over 24 hours with fever of 101
• Evaluation– Crackles R > L
– No peripheral edema
– Hypoxia (7.25/67/41 on 40% VM)
– Normal Echo
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27-year-old woman with dyspnea
• Clinical Course– FiO2 100%; PEEP 20 cm H2O
– Peak and plateau airway pressures: 40s
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27-year-old woman with dyspnea
• Clinical Course– FiO2 100%; PEEP 20 cm H2O
– Peak and plateau airway pressures: 40s
• Key questions– What is the cause of acute respiratory
failure?– How to oxygenate the patient?– How to save her life?
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Common Causes of Hypoxemic Respiratory
FailureAcute lung injury (ALI) / ARDS Pulmonary EdemaDiffuse alveolar HemorrhagePulmonary EmbolismInterstitial lung diseasePneumoniaNeoplasmPulmonary contusionAtelectasisCOPDAsthmaBronchiolitis
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ARDS: Berlin Definition
JAMA 2012;307:2526-33
Category CriterionTiming Within 1 week of clinical insult or
new/worsening respiratory sx
Chest Imaging Bilateral opacities – not fully explained by effusions, lobar/lung collapse, or nodules
Origin of edema Not fully explained by cardiac failure or fluid overload. Objective measure to rule out hydrostatic edema
Oxygenation: Mild 200 mm Hg < PaO2/FIO2 < 300 mm Hg*
Oxygenation: Moderate
100 mm Hg < PaO2/FIO2 < 200 mm Hg**
Oxygenation: Severe
PaO2/FIO2 < 100 mm Hg**
* PEEP or CPAP > 5 cm H2O; ** PEEP > 5 cm H2O
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• Di use bilateral ffinfiltrates– Patchy, confluent– Alveolar, ground- ‐
glass
• In contrast to CHF, no prominence of..– Cardiomegaly– Pleural e usionff– Widened vascular
pedicle
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ARDS: Chest Radiograph Criteria
• Radiographic findings not attributable to:– Chronic changes– Atelectasis– Mass– Pleural effusion
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Lung Compliance in ARDS
Normal
ARDS
Pressure
Vol
ume
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- primary vs secondary
• Primary - Direct lung injury (eg aspiration,
• pneumonia, contusion, inhalation)
– Patchy
– If it doesn’t evolve into SIRS/MODS,
Outcome better than secondary
ARDS Triggers
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- primary vs secondary
• Secondary - Lung is one of many organs • involved in SIRS/MODS (sepsis, pancreatitis,
hypotension)
– Diffuse – Outcome worse than primary
ARDS Triggers
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ARDS - clinical progression
STAGE DAYS XRAY PATHOLOGY
I Initiation Nl PMNs
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ARDS - clinical progression
STAGE DAYS XRAY PATHOLOGY
I Initiation Nl PMNs
II 1-2 days
Patchy PMNs, edema, Type I
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ARDS - clinical progression
STAGE DAYS XRAY PATHOLOGY
I Initiation Nl PMNs
II 1-2 days
Patchy PMNs, edema, Type I
III 2-10 days
Diffuse cell damage Exudate, Type II
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ARDS - clinical progression
STAGE DAYS XRAY PATHOLOGY
I Initiation Nl PMNs
II 1-2 days
Patchy PMNs, edema, Type I
III 2-10 days
Diffuse cell damage Exudate, Type II
IV >10 days
Diffuse proliferation Lymph,
fibrosis
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ARDS Mortality Trend
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ARDS Management
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ARDS: Blocking the trigger
•Appropriate infection management–Antibiotics–Surgical drainage–Foreign body removal
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ARDS - mediator modulation
• Failed trials• Coagulation cascade• Immuno-nutrition
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ARDS - blocking manifestations
•Goals are to “buy time” and avoid complications
•Support gas exchange/lung protective ventilator strategies
•Assure other components of DO2 are optimal
•Altering lung fluid fluxes
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ARDS Management
Mechanical Ventilation :
• Low TV (ARDSNET protocol)
•Unconventional approach:
• APRV• HFV
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ARDS ManagementMechanical Ventilation :
• Low TV (ARDSNET protocol)
•Unconventional approach:
• APRV• HFV
General Measures:
•Prone positioning
•Nitric oxide
•NMBA
•Fluid Management
•ECMO
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Ventilator Management
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ARDSNET N Engl J Med 2000;342:1301-8
Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and Acute Respiratory Distress Syndrome
861 Patients
429 Patients432 Patients
6 cc/kg 12 cc/kg
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http://hedwig.mgh.harvard.edu/ardsnet_old/justvent911/justvent911.html
ARDSNET: Setting the Ventilator
FiO2 .3 .4 .4 .5 .5 .6 .7 .7 .7 .8 .9 .9 .9 1 1
PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 18 20-24
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Hypothesis of ARDSnet 6 vs 12 Trial
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Brower et al, AJRCCM 2002;166:1515-17 Brower et al, AJRCCM 2005;172:1241-5
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General Measures
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Effect of Prone Positioning on Oxygenation
Gattinoni, et al. N Engl J Med 2001; 345:568-573
prone
Change in PaO2:FiO2 from baseline to 1h to end of period to next morning
supine
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• Multicenter RCT comparing prone (n = 237) and supine (n = 229) positioning in severe (P/F <150) ARDS
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– > 16 hr / d prone positioning
•Prone positioning associated with:– Lower 28 and 90 day mortality– More patients extubated at 90 days
– More ventilator-free days (at 28, 90 d)– No difference in complications
• Multicenter RCT comparing prone (n = 237) and supine (n = 229) positioning in severe (P/F <150) ARDS
Guerin et al. N Engl J Med 2013
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Inhaled Nitric Oxide
• Endogenous vasodilator
• Inhalation of 2 - 40 ppm produces selective dilation of pulmonary vessels
• Rapidly inactivated by combining with hemoglobin and by oxidation
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What is the Role for Nitric Oxide in ARDS?
• Oxygenation benefit for up to 4 days (5- ‐20ppm)
• No outcome benefit (survival, duration of mechanical ventilation, ICU LOS)
• Routine use of inhaled NO is not supported
• Potential role for inhaled NO as rescue therapy for severe refractory hypoxemia
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ECMO for ARDS
• Venovenous (VV- ‐ ECMO) for respiratory failure– Blood removed and
pumped through oxygenator and returned to circulation; no cardiac support
– Large vascular cannula, and coagulation, infection risk
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The Bottom Line
• Identify ARDS using conventional parameters (predisposition / timing, CXR, ABG)
• Use “lung protective approach” – 6 ml/kg PBW Vt
• Avoid trans-alveolar pressure > 30 cmH2O;
• Avoid cyclic alveolar collapse by applying PEEP, particularly for severe ARDS
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The Bottom Line
• Conservative fluid management: aim for balanced I = O
• Consider NMBA, prone positioning, NO, or ECMO for severe hypoxemia – moving from least invasive to most invasive.
• Prove that it helps to continue rx
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•Randomized, blinded controlled trial of methylprednisilone vs. placebo for ALI persisting > 7 days•2 mg/kg/day x 14 days; then 1 mg/kg/day x 7 days then tapered over 4 days.
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Methylprednisilone vs. placebo results
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Pressure vs Volume- ‐Targeted Ventilation in ARDS?
• No large, recent (low Vt) RCTs comparing only pressure vs volume- targeting‐
• Potential advantages of pressure- targeting‐– Easily adjust inspiratory time– Better patient- ventilator synchrony‐– Avoid regionally excessive transalveolar pressure
• Potential advantages of volume- targeting‐– Avoid high tidal volume, simplify implementation
MacIntyre & Sessler. Respir Care 2010; 55:43-55 Marini & MacIntyre Chest 2011; 140:286-294
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Mortality according to % of recruitable lung
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RM Techniques
CCM 2004:32:2371
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Mechanical Ventilation in ARDS: Prolonged Inspiratory Time
• Methods– Inspiratory Pause
– Decreased PIFR
– Prolonged TI
• Potential benefits– Higher mean pressure
– Autopeep
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• Impaired DO2
• Barotrauma
• Need for heavy sedation
• Doesn’t work
Mechanical Ventilation in ARDS: Prolonged Inspiratory Time
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Extended Inspiratory Time and Oxygenation in ARDS
Mercat A. et al., Crit Care Med 2001; 29:40
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ARDSNET N Engl J Med 2000;342:1301-8
Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and Acute Respiratory Distress Syndrome
Male IBW = 50 + 2.3(ht(in) - 60)
Female IBW = 45.5 + 2.3(ht(in) - 60)
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http://hedwig.mgh.harvard.edu/ardsnet_old/justvent911/justvent911.html
ARDSNET: Setting the Ventilator: Subtleties
• RR can be increased to correct pH• VT can be increased for
– Dyspnea and breath stacking (if PPl < 30)– PPl < 25 and VT < 6 ml/kg
• VT may go as far as 4 ml/kg if needed to keep PPl <30 cmH20
• Paralysis rarely needed (~6%)• Vast majority complied with protocol
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Eisner MD et al., Am J Resp Crit Care Med 2001; 164:225
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Ferring M, Vincent JL. Eur Respir J 1997; 10:1297-1300
Causes of Death in ARDS (%)
05
101520253035
MOF/Sepsis
Resp Card Neur Heme Ca
*
n=67
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Ferring M, Vincent JL. Eur Respir J 1997; 10:1297-1300
ARDS: Organ Failure(s) and Mortality
0
20
40
60
80
100
0 1 2 3 4 5
Mor
talit
y (%
)
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Headley et al., Chest 1997; 111:1306
Inflammatory Cytokines in ARDS (D1)
0
5
10
15
20
TNF IL-1 IL-8
pg/
mL
Survivors Nonsurvivors
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PFT's > 1 year after ARDS
DLCOTLCFVC
Pe
rce
nt P
red
icte
d110
100
90
80
70
60
Elliot, C.G. et al., ARRD 1987; 135:634
n=16
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PFT's In ARDS Survivors
Months After Extubation
129630
Pe
rce
nt P
red
icte
d90
80
70
60
50
40
FVC
TLC
DLCO
McHugh, L.G. et al., AJRCCM 1994; 150:90-94
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ARDS: AECC Consensus Definition
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Criticism
•Problems with the definition:
–PEEP not specified
–CXR criteria vague
•ALI vs ARDS: Does it matter?
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Lure, O.R. et al., Am J Respir Crit Care Med 1999; 159:1849
ALI vs ARDS: Does it Matter?
Characteristic ALI (n=66) ARDS (n=221)
P/F 239.8 ± 27.1 130.7 ± 37.5
Age 55.0 ± 19.8 61.3 ± 16.5
APACHE II 17.2 ± 7.9 19.2 ± 7.9
Quadrants on CXR 2.8 ± 0.8 3.0 ± 0.9
Mortality (90 d) 42.2% 41.2%
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Lung protection tradeoffs: PO2
Crs also better in the HIGH Vt group
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Lung protection tradeoffs: pH
ARDSnet rules allowed pH values as low as 7.15
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Unconventional vent. approach
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ARDS
–Unconventional approaches:
•Long I time strategies (APRV)
•HFOV
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APRV
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APRV Concerns:AutoPEEP & Tidal Volume Creep
Incomplete emptying (i.e. autoPEEP)
700
650
600
550
500
450
400
350
300
10pm 2am 6am10am
Tidal volume
6 ml/kg IBW
pressure
flow
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HFOV – CPAP with a “wiggle”
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HFOV for Severe ARDS
• Multicenter RCT of 548
patients of HFOV vs LTVV (Vt 6
ml/kg, high PEEP) for ARDS
(PaO2:FiO2 < 200
mmHg)
• Stopped early for harm
• HFOV associated with:
– Higher mortality (ICU, hosp)– More sedation, NMBA– More vasopressors– Less refractory hypoxemia
Ferguson et al. N Engl J Med 2013
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HFOV for Severe ARDS
• Multicenter RCT of 548
•
patients of HFOV vs LTVV (Vt 6
ml/kg, high PEEP) for ARDS
(PaO2:FiO2 < 200
mmHg)
• Stopped early for harm
• HFOV associated with:
– Higher mortality (ICU, hosp)– More sedation, NMBA– More vasopressors– Less refractory hypoxemia
• Multicenter RCT of 795 UK patients of HFOV vs usual care for ARDS (PaO2:FiO2 < 200 mmHg)
• – Vt = 8.3 ml/kg, PEEP 11 cm H2O
• No di erence in:ff– 30 day all cause mortality– ICU, Hosp LOS– Vent- ‐free days
Ferguson et al. N Engl J Med 2013
Young et al. N Engl J Med 2013
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ECMO for ARDS
• Extracorporeal Life Support (ECLS)
• Large RCT in UK :• lower mortality and/or disability in
group (but many other Rx di erences) ffPeek et al. Lancet 2009
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What PEEP should we choose? High or Low?
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Pressure vs Volume- ‐Targeted Ventilation in ARDS?
• No large, recent (low Vt) RCTs comparing only pressure vs volume- targeting‐
• Potential advantages of pressure- targeting‐– Easily adjust inspiratory time– Better patient- ventilator synchrony‐– Avoid regionally excessive transalveolar pressure
• Potential advantages of volume- targeting‐– Avoid high tidal volume, simplify implementation
MacIntyre & Sessler. Respir Care 2010; 55:43-55 Marini & MacIntyre Chest 2011; 140:286-294
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•Long term mortality depends on underlying health status (11% mortality in 1st year)
ARDS outcome
NEJM 2003; 348: 8
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•Long term mortality depends on underlying health status (11% mortality in 1st year)
•At one year:– 6 MW 49%, VC 85%, DLCO 72%– PTSD like syndrome–Are these long term effects of hypoxemia? hypotension? drugs ?
ARDS outcome
NEJM 2003; 348: 8
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Controversies in VILI - Overdistention
•Is it “maximal” stretch or “tidal” stretch (or both) that causes VILI?
–If “maximal” , goal is to keep Pplat <30 with any VT•Pplat < 30 is “safe”
–If “tidal”, goal is to reduce VT and Pplat to minimums•No Pplat is “safe”
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Stretch injury - Is it max stretch or tidal stretch?
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Controversies in VILI - Overdistention
•Is it “maximal” stretch or “tidal” stretch (or both) that causes VILI?
–If “maximal” , goal is to keep Pplat <30 with any VT•Pplat < 30 is “safe”
–If “tidal”, goal is to reduce VT and Pplat to minimums•No Pplat is “safe”
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Steroids in ARDS:• Use of low dose, longer duration steroids is
associated with more rapid recovery and may be associated with reduced mortality risk– But, small studies, methodological quality
issues
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Steroids in ARDS:• Use of low dose, longer duration
steroids is associated with more rapid recovery and may be associated with reduced mortality risk– But, small studies, methodological quality
issues
• If use steroids in ARDS– Avoid starting after day 14– Avoid NMBA– Infection surveillance– Methylprednisolone 2m g/kg/d, taper over 4
weeks
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ARDSNET N Engl J Med 2000;342:1301-8
Lower Tidal Volumes and Survival in ARDS